This invention relates generally to the field of pyridine chemistry with particular application in providing improved electrochemical processes for the reduction of cyanopyridine bases in commercially practicable flow cells.
Much attention has focused over the years on the reduction of nitriles, which are organic compounds containing the cyano radical "--CN." to their corresponding amines. The field of pyridine chemistry has been no less attentive than others in this regard, with the products of such reduced cyanopyridines, or pyridine carbonitriles as they are also called, exhibiting valuable uses in such applications as carbon dioxide scavengers, corrosion inhibitors, chelating agents, and others.
Historically, three approaches have been used to reduce these nitriles to their corresponding amines, those being catalytic hydrogenations, chemical reducing agents, and electrochemical reductions. In this regard, the ideal approach would be one that produces high yields of the primary amine using an inexpensive reducing agent, low temperatures, and not involving heavy demands on or uses of pollution control procedures. Reported successes approaching this ideal have been few, however, as the production of primary amines in good yields is often hampered by a pair of side reactions which occur during reduction. The first of these leads to the corresponding secondary amine as reported in H. Rupe, E. Hodel, Helv. Chim. Acta, 6, 865 (1923) and H. Rupe, W. Brentano, ibid., 19, 588 (1936). The second leads to hydrogenolysis of the amine to form the less-desired hydrocarbon as reported in J. Corse. J. T. Bryant, H. A. Shoule, J. Am. Chem. Soc., 68, 1907 (1946) and N. J. LeoSnard, G. W. Leubner, E. H. Burk., J. Org. Chem., 25, 982 (1960).
Catalytic hydrogenation procedures have suffered from both of these side reactions in addition to requiring undesirable elevated temperatures in most instances which promote thermal reacting leading to unwanted products and tars. In order to obtain satisfactory yields of primary amine, for example, trapping of the amine by an acetylating agent [F. E. Gould, G. S. Johnson, A. F. Ferris, J. Org. Chem., 25, 1658 (1960)]or the use of large quantities of ammonia [M. Rabinovitz in "The Chemistry of Functional Groups: The Chemistry of the Cyano Group" S. Patai, Ed, Interscience. N.Y. 1970, p. 321] has been required.
Active metal-reducing agents such as sodium in an alcohol solvent have also been reported, but once again with many accompanying problems [E. Bamberger, Ber., 20, 1703, 174 (1887)] which have prevented such methods from gaining general acceptance. Similarly, hydride-reducing agents have been reported to usually work well [N. C. Gaylord, "Reduction with Complex Metal Hydrides," Interscience, N.J., 1956 and S. Yamada, Y. Kikugawa, Chem. Ind. (London), 1967, 1325W , but require the use of an expensive reducing ag.RTM.nt. For that reason, such hydrides have been used only in special cases where the value of the product can support a high-selling price. In addition, the strongly basic nature of hydrides can initiate unwanted side reactions which have been a further complicating factor.
Some electrochemical procedures which have been reported seem to fulfill many of the desired features of an ideal nitrile reduction since low temperatures can be used, the electron is a very inexpensive reducing agent, and such methods normally do not place high demands on pollution controls. In the case of cyanopyridines, also referred to as pyridine carbonitriles, there have been many analytical studies particularly of the three isomeric monocarbonitriles.
For instance, L. P. Krasnomolova, A. E. Lyuts, V. I. Artyukhin, O. V. Agashkin, D. Kh. SembaeV, B. V Suvorov, Zh. Fiz. Khim., 52, 85 (1978) correlated the ease of reduction of such compounds at a mercury cathode with both the position of the long wave length ultraviolet adsorption band and the nitrile stretching frequencies in the infrared spectroscopy. Rafik O. Loutfy, Raouf O. Loutfy, Can. J. Chem., 51, 1169 (1973) also correlated ease of reduction with the n,.pi.*-triplet energies. The polarographic behavior of cyanopyridines has also been extensively studied and the mechanistic implications reported [J. Volke, R. Kubicek, F. Santavy, Coll. Czech. Chem. Commun., 25, 1510 (1960); V. A. Serazetdinova, B. V. Suvorov, O. A. Songina, Izv. Akad. Nauk Kaz. SSR, Ser. Khim., 18 (3), 64 (1968); V. A. Serazetdinova, B. V. Suvorov, O. A. Songina, Khim. Geterotsikl Soedin, (3), 327 (1973); V. A. Sarazetdinova, B. V. Suvorov, Nov. Polyarogr. Tezisy Kodl. Vses. Soveshch. Polyarogr., 6th, J. Stradino. ed., Zinatne, Riga, USSR 1975, p. 157; A. M. Kardos, P. Valenta, J. Volke, J. Electroanal. Chem., 12, 84 (1966); A. Kitani, K. Iida, K. Sasaki, Denki Kagaku, 41 (12), 900 (1973); J. Volke, V. Skala, J. Electroanal. Chem. Interfacial Electrochem., 36 (2), 383 (1972)].
However, there has been much less work reported on the preparative scale synthesis of these cyanopyridines by electrochemical means. For example, V. Krishman, K. Raghupathy, H. V. K. Vdupa, J. Electroanal. Chem. Interfacial Electrochem., 88 (30), 433 (1978) reported the successful reduction of 3-cyanopyridine in aqueous hydrochloric acid at a cathode having a palladium black deposit on a carbon base. The cell design in this case was a rudimentary beaker-type cell with a ceramic diaphragm thus having little or no commercial significance. The reported yield was good at about 80%, but current efficiency was moderate (about 40%). To achieve these results, however, the authors reported having to maintain the current density at less than or equal to about 20 mA/cm.sup.2, with higher densities resulting in poor yields and efficiencies.
Similarly, J. Volke, A. M. Kardos, Coll. Czech. Chem. Commun., 33 (8), 2560 (1968) reported reductions of all three isomeric mononitriles of pyridine under impractical conditions, with both the 2- and 4- isomers reportedly giving adequate results. In the case of 3-cyanopyridine, anomolous results were obtained. With all such experiments, however, Volke used very dilute solutions (10 mM) in a phosphate buffer at a mercury cathode, and in a standard beaker cell design. Also, product isolation was not done in this work, but yields were assessed analytically with Ninhydrin reagent. A cohesive mechanistic scheme was reported to account for the pH dependence and polarization behavior [J. Volke, V. Skala, J. Electroanal. Chem. Interfacial Electrochem. 36 (2), 383 (1972); J. Volke A. M. Kardos, Coll. Czech. Chem. Commun., 33 (8), 2560 (1968)]. Interestingly, there also seems to be some variance between V. Krishman, K. Raghupathy, H. V. K. Vdupa, J. Electroanal. Chem. Interfacial Electrochem., 88 (30), 433 (1978), which reported a synthetically useful reduction of 3-cyanopyridine, and others [A. M. Kardos, P. Valenta, J. Volke, J. Electroanal. Chem., 12, 84 (1966); J. Volke, R. Kubicek, F. Santavy, Coll. Czech. Chem. Commun., 25, 1510 (1960): J. Volke, A. M. Kardos, Coll. Czech. Chem. Commun., 33 (8), 2560 (1968)] which report polarographic results supporting nitrile cleavage instead of nitrile reduction. Thus, the correlation of results at very dilute and higher (more practical) concentrations is not good and the analytical reports do not accurately reflect synthetic scale results. In addition, Volke and Holubek [Coll. Czech. Chem. Commun., 27, 1597 (1963)] reported a spectroscopic identification of the product of 4-cyanopyridine reduction; however, the yield was not disclosed as a special apparatus was used and very small amounts of product were produced.
The synthetic work of the above references reporting electro-reductions of cyanopyridine isomers suffers from many common disadvantages. For example, only 3-cyanopyridine has been successfully reported to be reduced in kilogram-size quantities, the other isomers being reduced only in very small amounts [V. Krishman, K. Raghupathy, H. V. K. Vdupa, J. Electroanal. Chem. Interfacial Electrochem., 88 (30), 433 (1978)]. Even this large-scale reduction of 3-cyanopyridine, however, was done in aqueous hydrochloric acid which is corrosive, and required a specially prepared noble metal cathode which is expensive to produce. In this regard, mercury is the only other reported cathode material besides palladium o carbon.
Furthermore, all of this prior work has been performed in beaker cell designs which are acceptable for bench scale (0.01-1 Kg) and analytical experiments. but have no economic value for commercially practicable productions. There is no teaching or suggestion in any reference to applicant's knowledge that such electrochemical reductions of cyanopyridine bases have been or can be performed, or even attempted, using other cell geometries and techniques which may have commercial potential. There are three other references which bear on nitrile reduction, but provide very little, if anything, over the references already discussed [H. Lund, Acta Chem. Scand., 17 (8), 2325 (1963); M. Lacan, I. Tabakovic, J. Hranilovic, Z. Vajtner, R. Hranilovic, Croatica Chem. Acta, 44, 385 (1972); M. Lacan, et al., ibid, 43, 229 (1971)].